Avian Bornavirus and Proventricular Dilatation Disease: Facts, Questions, and Controversies

Key Points

  • Avian bornavirus has been shown to be a cause of the disease syndrome formerly known as proventricular dilatation disease or PDD.
  • Avian bornavirus is a labile virus, susceptible to most disinfectants, detergents, and ultraviolet light.
  • Birds can harbor asymptomatic avian bornavirus infection.
  • The avian bornavirus is intermittently shed in feces and urates.
  • Clinical disease develops secondary to the body’s response to infection, as lymphocytic-plasmacytic infiltrate develops in the brain, spinal cord, and peripheral nerves and is frequently described as neuropathic ganglioneuritis.
  • Progression of clinical disease, or neuropathic ganglioneuritis, can be slow or quite rapid.
  • The clinical signs of neuropathic ganglioneuritis typically vary from primarily gastrointestinal, primarily neurological, or both gastrointestinal and neurological.
  • Definitive diagnosis is challenging antemortem, but typically relies upon a combination of PCR and serology.
  • Whenever possible, isolation of infected birds is recommended; culling of infected birds is NOT recommended.

Introduction

Proventricular dilatation disease or PDD is one of the most frustrating conditions that avian practitioners, aviculturists, and bird owners encounter today. The recent discovery of avian bornavirus (ABV) as an etiological agent of PDD has not simplified the challenges. The detection of avian bornavirus infection is common in birds with PDD but the virus is detected in so many clinically healthy birds as well as birds with other chronic diseases that it is clear other factors along with ABV may be involved in development of disease.

Signalment and distribution

Proventricular dilatation disease was first reported in the late 1970s in macaws imported into the United States and Germany. During the early years, this disease was often referred to as “macaw wasting disease” (Payne 2012). Since that time, proventricular dilatation disease has been identified in over 50 different avian species including passerines like the canary (Serinus canaria), honeycreepers, weaver finches, waterfowl, toucans, birds of prey, and psittacine birds (Hoppes 2013, Payne 2012, Smith 2010, Weissenböck 2009). Proventricular dilatation disease has been reported in captive parrots in North America, Latin America, Europe, Australia, Africa, Japan, and the Middle East (Sassa 2013, Last 2012, Doneley 2007).

Pathogenesis

Avian bornavirus* (ABV), a newly discovered member of family Bornaviridae, was identified as a cause of PDD in 2008 (Payne 2012, Gancz 2009, Gray 2010, Gancz 2009, Honkavuori 2008, Kistler 2008). Avian bornavirus is a single-stranded RNA virus. The virus is intermittently shed in the droppings. Transmission is generally fecal-oral (Rinder 2009), however vertical transmission has also been demonstrated (Monaco 2012, Kerski 2012, Lierz 2011). The incubation period for ABV infection can be as brief as days but it has also been hypothesized to be much longer, possibly decades, in some birds.

There are ten known ABV genotypes and seven of these genotypes can affect psittacine birds. The virulence of these genotypes can vary, and there is also evidence that an asymptomatic bird harboring one genotype can sometimes become clinically ill after exposure to a second, novel genotype (Rubbenstroth 2013, Nedorost 2012, Lierz 2012, Rinder 2009).

*Editor’s note:  Avian bornavirus in psittacine birds is more accurately described as parrot bornavirus.

 

Clinical disease

Proventricular dilatation disease is more accurately described as neuropathic ganglioneuritis, lymphoplasmacytic ganglioneuritis, or avian autoimmune ganglioneuritis. Clinical disease arises when the host mounts an immune response that leads to progressive destruction of brain, spinal cord, and peripheral nerves via lymphocytic-plasmacytic infiltrate. Nerves that supply the proventriculus, ventriculus, and intestines are commonly affected.

Progression of clinical disease can be slow or quite rapid. The clinical picture may be primarily gastrointestinal, primarily neurological, or both. (Table 1) (Fig 1, Fig 2). Polyuria, hypotension, and cardiac abnormalities have also been reported. Avian bornavirus infection damages the Purkinje cells, which can potentially cause arrhythmias however this is usually a postmortem finding.

Table 1. Potential signs of neuropathic ganglioneuritis in the psittacine bird
Gastrointestinal singsCentral or peripheral nervous system signs

  • Ataxia, weakness

  • Proprioceptive deficits

  • Tremors

  • Seizure activity

  • Blindness

  • Abnormal head movements

  • Peripheral neuritis

Maldigestion/malabsorption diarrhea in a parrot fed a seed-based diet.

Figure 1. Maldigestion/malabsorption diarrhea in a parrot fed a seed-based diet. Photo credit: Dr. Gregory A. Rich. Click image to enlarge.

Radiographic evidence of proventricular dilatation (arrow).

Figure 2. Radiographic evidence of proventricular dilatation (arrow). Photo credit: Dr. Sharman Hoppes. Click image to enlarge.

*Editor’s Note: Although death would seem to be the most objective of parameters, there are camps of PDD study that disagree vehemently with the statement that symptomatic avian bornavirus disease is invariably fatal and there are reports of birds with chronic disease living long, long lives.

Antemortem diagnosis

Definitive diagnosis of neuropathic ganglioneuritis remains challenging. There are birds at the Schubot Exotic Bird Health Center that have tested positive for ABV via PCR and serology for over 7 years that continue to be clinically healthy. Other individuals consistently tested negative for up to 6 years before becoming acutely ill. These birds only tested positive on PCR and serology at the terminal stages of disease.

PCR: Reverse transcription (RT) polymerase chain (PCR) testing of droppings, feathers, and blood has been evaluated in psittacine birds (Table 2) (Hoppes 2013, de Kloet 2011, Dahlhausen 2010). Positive ABV PCR test results do not mean the bird has or ever will develop clinical disease, and most PCR testing does not differentiate between ABV genotypes. Due to intermittent shedding, one negative PCR test result also cannot rule out ABV infection, particularly if the sample is not properly stored.

Serology: Serological testing has also been frustratingly inconclusive, with some ABV-infected birds failing to develop a detectable antibody response within weeks of dying of neuropathic ganglioneuritis (Table 2) (Herzog 2010). In other individuals there appears to be a positive correlation between the level of antibodies produced and the development of disease. Tests used to detect ABV titers have included indirect immunofluorescence, ELISA, and Western blot assay (Hoppes 2013).

Recommendations based on current practices at Schubot: A combination of cloacal or feather RT-PCR with a serologic assay may offer the best chance of identifying ABV infection. Birds with a high ABV load via PCR combined with high antibody titers appear to have the highest risk of developing clinical disease (Heffels-Redmann 2012), however there is there is no one combination of tests that can be used to reliably predict the progression from ABV exposure and shedding to clinical disease at this time. Multiple tests must be performed before a bird can be considered ABV negative. Ideally three negative PCR test results are needed for a bird to be considered negative.

See Questions and Controversies below for additional antemortem diagnosis recommendations.

Table 2. Laboratories in the United States that perform avian bornavirus diagnostic testing
PCRSerologyAntiganglioside antibody
Avian BiotechXX
The Schubot CenterX
Veterinary Molecular DiagnosticsXX

The apparently healthy ABV-positive bird

There is evidence that ABV is endemic in parrots in the United States, with screening of some homes and aviaries revealing infection rates of 33% to 60% in clinically healthy birds. Considering the difficulty of testing and the intermittent shedding of the virus, these infection rates for exposed birds are likely higher than what is reported.

The significance of low or inconsistent antibody levels and low PCR responses remains unclear; however there have been cases of even brief exposure resulting in clinical disease.

Current recommendation: Isolate a single ABV-positive bird from other susceptible individuals since the virus is intermittently shed in the feces and urates. Despite this advice, there have been many instances where an infected bird has been housed in direct contact with negative birds for months or even years without apparently transmitting disease. At this stage in our understanding of the disease, it is impossible to predict if individuals housed with positive birds will become positive or clinically ill. A recent study has concluded that horizontal transmission of ABV by direct contact is inefficient in immunocompetent fully-fledged domestic canaries and cockatiels (Nymphicus hollandicus). Birds in this study were followed over a 4-month period (Rubbenstroth 2014).

Recommendations based on current practices at Schubot: Determine the genotype in ABV-positive birds and keep birds with different genotypes separate. There is evidence that different genotypes differ in virulence and in the studies performed so far, one genotype is not protective against infection with another ABV genotype. In fact there is evidence that exposure to a novel ABV genotype can be pathogenic in a bird currently harboring ABV without illness. Therefore housing one ABV positive bird does not mean an owner can take in other positive birds without risk (I. Tizard, oral communication, March 2014).

There are no recommendations to automatically cull or euthanize infected birds. A clinically healthy positive bird may live its entire life without ever developing clinical disease.

Postmortem diagnosis

Gross necropsy findings in the bird with neuropathic ganglioneuritis may include profound emaciation as well as a dilated proventriculus, ventriculus, and/or intestines (Fig 3).

Profound emaciation in a cockatoo with neuropathic ganglioneuritis

Figure 3. Profound emaciation in a cockatoo with neuropathic ganglioneuritis. Photo credit: Dr. Isabelle Langlois. Click image to enlarge.

Histopathologically there may be a lymphoplasmacytic ganglioneuritis involving the brain, spinal cord, peripheral nerves, splanchnic nerves, heart, and adrenal gland. In some instances, lesions can also be detected in the lungs or kidneys. Lesions may only be present in the brain and spinal cord in some neurologic cases.

Avian bornavirus can consistently be detected by PCR analysis in the tissues of birds that die of neuropathic ganglioneuritis. The virus may be found in all major organs or may be limited to the brain, spinal cord, and peripheral nerves. The vitreous humor can also be a source of ABV, even in apparently healthy carrier birds (Hoppes 2013).

Management of disease

Given the inflammatory infiltrate that develops, nonsteroidal anti-inflammatory agents like celecoxib (Celebrex, Pfizer) and meloxicam (Metacam, Boehringer Ingelheim) have long been offered to affected birds. Unfortunately neither meloxicam nor the immunosuppressive drug cyclosporine has slowed the progression of disease in birds experimentally infected with ABV at Schubot Exotic Bird Health Center. The Center is currently evaluating cyclosporine and the antiviral agent, ribavirin (Rebetol, Merck) but further study is needed (Hoppes 2013).

Visit Questions and Controversies below for additional information.

Prevention or control

Bornavirus is easily destroyed in the environment, and it is susceptible to most detergents, disinfectants, and ultraviolet light.

Although isolation of the ABV-positive bird is recommended, some bird owners have successfully maintained a group of birds that include a positive individual. The risk of disease transmission is reduced when owners offer a good plane of nutrition; provide exemplary husbandry and adequate ventilation, while minimizing stress, employing scrupulous hygiene practices, and basic biosecurity measures.

Biosecurity measures that reduce the risk of disease transmission

  • Wash hands between birds
  • Use a footbath or disinfect shoes when going from infected to non-infected rooms
  • Care for ABV-negative birds before handling positive birds

Since it has been shown that ABV can be vertically transmitted, incubator hatching does not definitively halt the spread of infection to the chick  (Monaco et al 2012, Lierz et al 2011).

Questions and controversies

    • When a bird tests positive for ABV on various antemortem tests does this mean the bird has the disease syndrome called proventricular dilatation disease (PDD)?

The detection of ABV infection is common in birds with PDD but ABV infection may occur without clinical evidence of disease or ABV-positive birds can also suffer from other chronic diseases.

    • Is ABV the only cause of PDD?

Although a causal relationship between ABV infection and PDD has been confirmed, ABV has not been confirmed as the one and only cause of this syndrome.

    • Is ABV a cause of PDD?

Feather destructive behavior is sometimes seen in birds with ABV infection (Horie 2012). Feather picking and self-mutilation can be observed with any bird with systemic illness, however this feather damaging behavior has also been theorized to occur secondary to peripheral neuropathy.

    • Is clinical ABV infection invariably fatal?

Although death would seem to be the most objective of parameters, there are camps of PDD study that disagree vehemently with the statement that symptomatic ABV disease is invariably fatal. There are reports of birds with chronic PDD disease living long, long lives, however much of this controversy may stem around confirmation of disease. Was ABV infection confirmed in these cases or was PDD diagnosis based on clinical signs and radiographs only?

    • What other antemortem tests can be performed in the diagnosis of PDD and are there additional considerations for discussion?

Since serologic test results for ABV infection are sometimes poorly correlated with clinical disease, additional tests include:

      • Antiganglioside antibodies: Birds with clinical disease demonstrate elevations in antiganglioside antibodies regardless of PCR test status, and antiganglioside antibodies have been reported to show very good correlation with the presence of histopathologic lesions (B. Dahlhausen, email communication, July 2014).
      • Histologic evaluation of crop biopsy: Surgical removal of a small, vascular, full thickness segment of the crop wall can be used to identify histologic signs consistent with neuropathic ganglioneuritis (Gregory 1996). Crop biopsy results depend on the presence of segmental disease in the tiny piece of tissue collected. Therefore positive results support a diagnosis of PDD, however negative results have very little meaning (Lierz 2009). Most birds without gastrointestinal signs are almost always negative via crop biopsy.
    • What can be done for the PDD patient?

Although research out of Schubot Exotic Bird Health Center has shown dismal results with the use of meloxicam in cockatiels infected with ABV (Hoppes 2013), anecdotal reports suggest the use of cyclooxygenase (COX)-2 inhibitors may be helpful in some clinical cases (B. Dahlhausen, email communication, July 2014). Positive results have been reported with the pure COX-2 inhibitor, celecoxib. Reported dose ranges vary but typically start at 10-20 mg/kg PO SID to BID. As a COX-2 preferential inhibitor, results with the use of meloxicam (0.5-1 mg/kg PO SID) have been more unpredictable. Most recently positive results have been reported with robenicoxib (Onsior, Novartis) (1 -2 mg/kg IM) paired with immunomodulation therapy in the form a scheduled injection of Mycobacterium bovis inoculum to redirect and ultimately desensitize the bird’s immune system, similar to the management of Guillain–Barré syndrome in humans (Rossi 2013).

Summary

Although avian bornavirus infection is common in clinically healthy birds, the development of clinical disease is more rare. Symptomatic disease, commonly called neuropathic ganglioneuritis or proventricular dilatation disease, is a progressive, potentially fatal neurological disorder of psittacine birds caused by avian bornavirus. This complex syndrome can present with diverse clinical findings including weight loss, proventricular dilatation, and/or neurological signs. Currently there is no one combination of tests that can be used to reliably diagnose ABV infection and there is no cure, however current recommendations will change as our understanding of this disease continues to grow.

References